The primary effort on this project has been focused upon laboratory setup and personnel acquisition. I began as an NCI Investigator on August 26, 2003, having previously been a Senior Staff Investigator and dermatologist at the Henry Ford Health System in Detroit for 4 1/2 years. In the short time that I have been at NCI, I have supervised the continued work of a Visiting Fellow, Diwakar Ganesh, who worked with me at Henry Ford, as well as the work of Shunlin Jiang, a biologist who joined the lab on September 22. We have procured major equipment for the lab and initiated lab processes that will be important for our future. Diwakar's work was presented in poster form in early September at the annual meeting of the Pan-American Society for Pigment Cell Research, where I also presented a talk on work done at Henry Ford about melanocyte function and survival in the inner ear. Additionally, I have made two presentations at NIH, one to the Stanley group inter-PI lab meeting on September 30 and one to the NIH Pigment Cell Interest Group on October 7. In the lab, we have begun work to develop a transgenic mouse line that will permit us to express in an inducible manner altered signaling proteins in vivo in melanocytes. We have also begun to investigate the expression and mutation status of the signaling protein B-Raf in commonly used melanocyte and melanoma cell lines. This combination of approaches should help us understand more about the role of Ras- and B-Raf-dependent signaling in normal melanocyte development and differentiation. It should also provide a foundation for examining directly the importance of B-Raf activity in melanoma progression in mice, a topic we have been prompted to pursue based upon the finding that B-Raf mutations are extremely common in both human melanomas and human melanocytic nevi.